Editor’s note: This is our first interview feature on HCMBeat. In the future, we hope to feature more interviews with other HCM researchers who have published articles of interest to the HCM community.

By now, you have probably already heard the buzz about RESET- HCM – a study about the effects of exercise on HCM patients conducted by Dr. Sara Saberi and Dr. Sharlene Day at the Hypertrophic Cardiomyopathy Clinic of the University of Michigan’s Frankel Cardiovascular Center in collaboration with Dr. Matthew Wheeler and Dr. Euan Ashley of Stanford’s HCM Center. The findings were presented at the American College of Cardiology Conference on March 17, 2017 held in Washington D.C. and were the subject of this feature on HCMBeat.

Recently, Cynthia Waldman of HCMBeat had the opportunity to sit down with Drs. Saberi and Day for a detailed conversation (over Skype) about the study. What follows is a transcript of their conversation (which has been edited for readability).

HCMBeat: What was the genesis of the RESET-HCM study?

Dr. Day: We wanted to gather the first evidence that exercise could potentially be beneficial for HCM patients.

We know that exercise is good for everyone, including individuals with various forms of heart disease. However, HCM patients are often told not to exercise because of a potential risk for sudden cardiac death. This paradox came up time and time again with virtually every patient with HCM that we saw. There were a number who had given up sports or recreational activities that they really had enjoyed and it had a major negative impact on them. When we referred to the existing guidelines, we realized that there was no evidentiary basis for any of the guidelines’ recommendations and that it was really unclear what kind and intensity of exercise HCM patients should be doing and what the level of risk was for these patients. That was really the motivation behind our study. We felt like learning about the benefits and potential risks of exercise was something that could potentially impact every HCM patient.

As the first clinical trial to investigate exercise in HCM, we were primarily focused on showing the benefit of moderate intensity exercise, similar to what has been shown in patients with other heart conditions, such as those with congestive heart failure. Indeed, we observed that HCM patients who exercise over a period of 4 months had improved exercise capacity compared to those who didn’t. This was really exciting to us, to show for the first time that exercise benefits patients with HCM. Because arrhythmias that can cause sudden death occur rarely and randomly, our study couldn’t definitely address safety over longer periods of regular exercise. However, no major adverse events occurred in any of the participants in the study. There are ongoing registries which will address these safety concerns in the future, but at least we can say that we saw no harm from moderate intensity exercise in our study.

Dr. Saberi: When we are seeing patients in clinic, they really do have a fear that is palpable around exercise and physical activity. And for some it is really paralyzing. I distinctly remember a patient who told me that she would actually become fearful that she was doing something that would hurt herself and her heart because she would become aware of her heart rate increasing as she was running up and down the stairs in her house doing laundry. We felt strongly that we needed to have more data so that people would not have to live with that kind of fear in their daily lives.

HCMBeat: Who participated in the study? How did you enroll participants?

Dr. Saberi: We collaborated with Stanford, and most participants came either from the patients already seen at Stanford or U. Michigan’s HCM programs. A small number saw the study on the ClinicalTrials.gov website and contacted us that way. The people who contacted us from outside our institutions already had some interest in exercise. We found that this interest motivated them to contact us because they were interested in getting more information and guidance about what type and how much exercise was safe for them to participate in.

HCMBeat: What was the design of the study?

Dr. Day: We divided the participants into two groups: a “Usual Activity Group” who continued with the same level of activity that they were already accustomed to and an “Exercise Training Group” whose activity level was increased from whatever their baseline activity level was. Activity was increased steadily over the course of 4 weeks with regard to one or more of three categories: 1) duration; 2) intensity; and 3) frequency. The idea was to make a change from their baseline activity level.

HCMBeat: How did you decide whether a person would be in the exercise group or the control group? Were regular exercisers assigned to the exercise group?

Dr. Saberi: The participants in the study ran the full gamut from sedentary to regular exercisers. Some did not do any exercise at all while others ran 5 to 6 miles a day at baseline. No one was assigned to a group based upon their baseline activity level. Everyone in the usual activity group was instructed to continue their baseline activities and habits. No one was told to be a couch potato. The difference was that the usual activity group members did not meet with an exercise physiologist and did not get any guidance regarding exercise from the study organizers.

Dr. Day: Randomization is very important in clinical trials because it ensures that there is no bias in the study. For example, if we were to take everyone that was already exercising and place them in the exercise group, it would not be a valid study. Randomization was done anonymously by a computer program. We did take into account sex, age, and whether or not the patient had outflow tract obstruction so that we could make sure that these factors were equally represented in both groups.

HCMBeat: Did you note any differences between patients who were obstructed and those who were not obstructed?

We had equal numbers of obstructed and non-obstructed patients in each study group. We also had equal numbers of patients who had undergone septal myectomy or alcohol septal ablation in each group. We are still analyzing the data, so we have not yet determined whether there was a difference in the increase in functional capacity between obstructed and non-obstructed patients. We plan to do more analysis of the results to figure out what characteristics constituted the group of responders vs. the non-responders.

HCMBeat: Did you see any negative results at all from the trial?

Dr. Saberi: No, there were no major adverse events in either group, and no difference in the incidence of minor, non-life-threatening arrhythmias between the 2 groups. There were also no differences in the amount of muscle thickening or scar formation over the course of the study.

Dr. Day: There were no defibrillator firings, no sustained ventricular arrhythmias and no cardiac arrests. And while there were incidents of non-sustained VT and other atrial arrhythmias, there were no differences between the two groups and many of these patients had these arrhythmias when the trial started. Very few had any new onset of arrhythmias.

HCMBeat: Did you notice any psychological benefits to the patients who exercised?

Dr. Saberi: The only way in which we really quantified psychological benefit was in 3 different quality of life surveys. We noted some significant improvement on those surveys which assessed a patient’s physical limitations. We saw an 8-unit improvement in the Exercise Group over the Usual Activity Group (5 units is considered to be clinically significant). There was also a 5-unit increase in the global health self-assessment by study participants. We didn’t see any negative effects in terms of mental, emotional or physical health perceptions in the patients.

Anecdotally, I definitely heard from people who participated in the study who said that they felt better. Some also lost a significant amount of weight and thought that the weight loss made them felt better as well.

HCMBeat: What specific types of exercise were people doing?

Dr. Saberi: They did what they were able to do and what was accessible to them. The Exercise Group met with an exercise physiologist who discussed which type of exercise was easiest and available for each participant to do. Activities included things such as walking, running, swimming, elliptical trainers, rowing and stair climbing.

Dr. Day: The prescription for exercise was individualized for each study participant. It was not the same for everyone. Each person had a written exercise prescription with their own target heart rate that was based on their stress test. It was not an arbitrary heart rate of 140 or 150 bpm for example. It was based on what their heart rate was normally and what their peak heart rate was on their stress test. And then we targeted 60% to 80% of their peak heart rate. And it was also based on what they were doing before the study. So, if they were doing nothing at all, then we would start them out with shorter duration and build them up to a moderate level of exercise over 4 weeks which they maintained for the remainder of the study.

Each person was different. I think that is a very important message from the study. Arbitrary cutoffs for heart rate, duration or intensity don’t make a lot of sense. Individuals may have some limitations from their HCM and others have different goals for what they want to achieve. So, I think it is important to individualize the exercise program for each person.

HCMBeat: Do you have any plans to look at isometric exercise and its advisability and safety in HCM?

Dr. Day: Isometric exercise has different levels of intensity. It also requires a person to go to a gym if they don’t have the equipment at home. Safety is very difficult to address and I am not sure if we would be able to assess safety in a randomized clinical trial because of the rare and infrequent nature of these events. I think it would be very difficult to build into a study protocol. It’s a great question and we certainly get that question a lot from patients. We will have to think more about how we might incorporate isometric exercise into future studies.

HCMBeat: Have you noticed a reluctance from physicians to recommend exercise to their HCM patients? How would you advise physicians to counsel their HCM patients are a result of this study?

Dr. Saberi: No non-invasive interventions have been shown to affect disease course in hypertrophic cardiomyopathy to date. We found that exercise improves functional capacity in HCM patients. Since reduced functional capacity has been associated with worse outcomes in HCM and progression to heart failure, it is important that we were able to show that habitual, moderate intensity exercise that is easily feasible and accessible for everyone with HCM could make a difference in functional capacity. And we didn’t see any evidence of harm. Therefore, we recommend that a patient with HCM should exercise for their general health, just as we would recommend the same for a patient with chronic heart failure, diabetes, or peripheral vascular disease. This study is the first to show that there are true benefits to be gained from exercise in patients with HCM. Patients with HCM are not immune from the negative effects of a sedentary lifestyle. There is nothing about them that protects against coronary artery disease, obesity, sleep apnea, diabetes, dyslipidemia or hypertension, and all of these other conditions reduce quality of life and shorten lifespan. Anything we can do to encourage our patients to pursue a lifestyle that helps them live longer with better quality is fantastic. I think that this study shows that exercise may be that intervention.

Dr. Day: We do encounter many patients that come to see us who have been told by other doctors that they should do nothing and that they shouldn’t exercise at all. That is not what the guidelines say, but I think that due to the uncertainty, there is over-interpretation of the potential negative effects of exercise that have not been proven. We are really hopeful that this study will change practice. That was our goal. We want all patients with HCM to be able to enjoy a healthy lifestyle.

HCMBeat: How would you suggest that physicians and patients implement your recommendations?

Dr. Saberi: I think that it is a good idea to do a monitored treadmill stress test where you can see heart rate and blood pressure response and you can see how far a person can push themselves. It is important in individualizing a prescription to know how the heart rate responds to the various medications patients take every day. It doesn’t have to be cardio-pulmonary stress testing. That is what we chose from a research perspective, but a simple treadmill stress test that is available to just about any family practitioner, internist or cardiologist would certainly suffice.

Dr. Day: The exercise physiologists are very well attuned to the protocol and tailoring the intensity level of the exercise test to the baseline level of activity for that patient and what their physical limitations may be. There are some standard protocols out there that are commonly used in exercise tests in stress labs. We have chosen one that has 20 different intensities in terms of how fast the treadmill goes, what the incline is, and how long the stages last. We have found that to be very useful in tailoring the test for the patient so that it is not too hard or too easy. We also use the data from the test itself to devise the exercise program. Now that the study is over, we are looking into implementing standard consultations for our patients with an exercise physiologist.

HCMBeat: Given that it may not be possible for patients to consult with an exercise physiologist or to do a stress test before starting out with an exercise program, can you recommend other ways HCM patients and their physicians might be able to come up with a personalized exercise program?

Dr. Day: There are going to be barriers to implementing the routine stress test as well as the time that it takes to individualize exercise programs, but at least there are some guidelines in the methods of the manuscript that could be implemented fairly easily without an intensive hour-long consultation. Heart rate monitors are readily accessible now and devices that track heart rate can be very helpful for the patient. Really just taking a simple calculation of what their heart rate reserve is, based on their heart rate during the stress test, and giving that to them as a guide as to where their heart rate should be when they are exercising. Also, providing the patient with a perceived exertion scale, so that they know that if they are breathing and/or working hard and they don’t think that they can continue for another minute, then they should drop back so that they can increase the duration. I think that there are some simple things that can be incorporated into routine patient visits that wouldn’t require a detailed exercise consultation.

HCMBeat: Do you have any other words of wisdom about how you help your own patients incorporate exercise into their lives?

Dr. Day and Dr. Saberi: We participate in a shared decision making model where we just want to make sure that whatever our patients are doing, we can make it as safe as possible for them so they can be prepared for any eventuality. Whether that is AEDs on site, teaching them to heed warning signs and to listen to their body, making sure that they stay hydrated, having an exercise partner, having your cell phone handy, etc. All of these things help to make the exercise experience safe and enjoyable for our patients.

HCMBeat: Dr. Day and Dr. Saberi – I would like to thank you on behalf of the entire HCM community for taking the time to discuss your work today. This has been so informative and will be a great resource for HCM patients and doctors alike.

About Dr. Saberi: Sara Saberi is an Assistant Professor in the Division of Cardiovascular Medicine and a member of the Inherited Cardiomyopathy Program at the Frankel Cardiovascular Center. She received her bachelor’s degree from Northwestern University and her medical degree from Wayne State University. She obtained her residency training in Internal Medicine and fellowship training in Cardiovascular Medicine at University of Michigan and permanently joined the faculty at Michigan in 2010. Dr. Saberi’s clinical work is focused on providing comprehensive care to patients with genetic cardiomyopathies and their families. Her research work focuses on clinical research aimed at learning more about inherited cardiomyopathies and development of new treatments to prevent or delay onset or progression of disease. One of her areas of focus is determining the impact of exercise training on outcomes, disease features, and quality of life in patients with hypertrophic cardiomyopathy and establishing evidence-based guidelines to inform recommendations for athletes with cardiomyopathies.

As someone who benefits both physically and emotionally from light and moderate-intensity exercise (she enjoys yoga, weight-training, jogging, elliptical, and cycling) and loves to be outdoors hiking or biking, Dr. Saberi wants her patients to be able to enjoy the same benefits. No races for this doctor – exercise-induced asthma has always been a challenge!

About Dr. Day: Sharlene Day graduated from the Massachusetts Institute of Technology and received her medical degree from New York University School of Medicine. She completed her internal medicine residency and cardiovascular medicine fellowship at the University of Michigan. Soon after completing fellowship and postdoctoral research training, Dr. Day started a dedicated program for treating patients and their families with hypertrophic cardiomyopathy (HCM) in 2007 that is now one of the largest in the U.S. While continuing to provide comprehensive care to patients with HCM and their families, the program has also broadened its focus to include evaluation and treatment of other genetic heart muscle conditions. Dr. Day and her colleagues are actively involved in institutional and multi-center research studies that aim to learn more about inherited cardiomyopathies, and to develop new treatments to prevent or delay the onset of symptoms or reduce their severity. Dr. Day is also very interested in the underlying biology of heart muscle disorders and leads an active laboratory that uses various models systems, including human heart muscle cells that are derived from stem cells, to identify important factors that cause the disease to develop and progress over time. While the research feeds her scientific curiosity and the hope to make a real difference in developing new treatments for these conditions, it is the day to day interactions with her patients and their families that she finds most gratifying and rewarding.

As a runner and triathlete herself, Dr. Day recognizes the importance of healthy eating and regular exercise. A major focus of her research is determining the impact of fitness on quality of life and outcomes in patients with HCM, and establishing evidence-based guidelines to inform recommendations for athletes with cardiomyopathies.

What is HCM?

HCM is a very common condition, and may affect as many as 1 in 200 people. However, many do not know that they have the disease and are often undiagnosed or have instead been misdiagnosed with other conditions.

The scariest thing about HCM, and the most sensational, is that HCM can sometimes cause sudden death, and this can occur without obvious symptoms beforehand.

Luckily, recent research has shown that with the right treatment, and thanks to modern medical advances, the scariest and worst scenario is not likely, and that most HCM patients will live normal life spans with few disabilities.